Dendritic patterning by interacting extrinsic cues

通过相互作用的外部线索形成树突图案

• 批准号: 8505789
• 负责人: Wesley B Grueber
• 金额: $ 34.77万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-01 至 2018-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8505789
• 关键词: Ablation; Afferent Neurons; Axon; Behavior; Cell surface; Cells; Cues; Data; Defect; Dendrites; Development; Disease; Drosophila genus; Elements; Ensure; Epidermis; Erinaceidae; Genes; Growth; Health; Human; Invertebrates; Knock-out; Lasers; Mediating; Molecular; Morphogenesis; Morphology; Nerve; Nervous System Physiology; Nervous system structure; Neurons; Pattern; Positioning Attribute; Presynaptic Terminals; Publishing; Reporting; Research; Role; Sampling; Sensory; Signal Transduction; Signaling Molecule; Sister; Study models; Substrate Interaction; Synapses; System; Testing; Work; base; gene function; insight; loss of function; morphogens; nervous system disorder; neuronal patterning; novel; programs; public health relevance; receptor; research study; sensory system; smoothened signaling pathway; transcription factor; two-dimensional

DESCRIPTION (provided by applicant): The territories of dendritic and axonal arbors determine how neurons receive and transmit information in the nervous system, and disruptions of dendritic and axonal morphology are associated with numerous neurological disorders. Many types of dendrites and axons are organized according to the principles of tiling and self-avoidance, in which arbors of neurons expand until they abut neighboring arbors. Both self-avoidance and tiling ensure that sensory or synaptic inputs in the nervous system are sampled completely and non-redundantly, a critical requirement for functional neuronal circuits, however we still know little about how such territories are built. We propose to examine the mechanism of dendritic tiling in the Drosophila sensory system, a powerful model for studies of the molecular control of neuronal morphogenesis. We propose to examine the molecular basis for dendrite-dendrite interactions and dendrite-substrate interactions that control tiling behavior of dendrites To accomplish our aims we will perform laser cell ablations to eliminate neurons and their dendrites to determine whether dendrite-dendrite interactions are important for field formation. We will use gene knock out approaches to eliminate the function of genes and assess necessity for tiling, and, conversely, misexpress genes to determine whether they are sufficient to promote tiling. We will study the re-use of signals that are important for dendritic tiling during axon tilng to explore whether dendrites and axons are patterned by similar cellular and molecular mechanisms. We expect that these results will be highly relevant for understanding the mechanisms by which proper dendritic and axonal patterning is achieved in the nervous system, and how alteration or disruption of molecular programs might underlie developmental defects.

描述（由申请人提供）：树突状和轴突轴的领土决定神经元如何在神经系统中接收和传输信息，以及树突状和轴突形态的破坏与许多神经系统疾病有关。许多类型的树突和轴突是根据瓷砖和自我避免的原理组织的，在这种原理中，神经元的乔木扩展，直到它们毗邻附近的乔木。自我避免和瓷砖都确保神经系统中的感觉或突触输入被完全和非重新采样，这是功能性神经元电路的关键要求，但是我们仍然对这些领域的建造方式知之甚少。我们建议检查果蝇感觉系统中树突状平铺的机制，这是研究神经元形态发生的分子控制的强大模型。我们建议检查树突形成岩石相互作用和树枝状底物相互作用的分子基础，以控制树突的瓷砖行为以实现我们的目标，我们将执行激光细胞消融，以消除神经元及其树突以确定树突形成对树突形成是否重要。我们将使用基因敲除方法来消除基因的功能并评估平铺的必要性，相反，misexpress基因确定它们是否足以促进平铺。我们将研究对轴突期间树突状瓷砖很重要的信号的重复使用，以探索树突和轴突是否是通过相似的细胞和分子机制模式化的。我们预计这些结果将与理解在神经系统中实现适当的树突状和轴突模式的机制高度相关，以及分子程序的变化或破坏如何构成发育缺陷的基础。